p53 is a negative regulator of cell division. Mutations in p53 are far and away the most frequent genetic lesions encountered in human cancers, appearing in 50% or more of tumors analyzed. These findings raise the intriguing possibility that mutant p53 could be a useful marker for human cancers. We have developed a sensitive quantitative immunometric assay (ELISA) selective for mutant p53 proteins. The assay will be used to measure mutant p53 in serum from human subjects. Data will be evaluated to determine if a significant correlation exists between the levels of mutant p53 measured in the serum and any underlying neoplastic condition. Samples will be obtained from patients with either breast carcinoma (site #1) or cancer of the head and neck (site #2) and also from matched cancer-free controls. Statistical evaluation of the results from coded samples will be analyzed with respect to diagnostic potential. Where possible, a biopsy of the tumor will be obtained, evaluated for the presence of p53 overexpression using immunohistochemical techniques, and the results correlated with the serum data. In Phase II, multi-site pre-clinical evaluations will be conducted on a greatly expended patient population. In addition, the assay would be adapted for use on an automated clinical instrument. Rapid quantitation of serum mutant p53 should facilitate research on the clinical significance of p53 and could improve the specific diagnosis, prognostic evaluation and monitoring of human cancers.